Introduction. The synthesis of focused, chemical libraries provides incentive and inspiration for the discovery of novel chemical reactions. Scaffold rearrangement is an attractive approach for library development due to the rigid structures that scaffolds can possess and the stereochemical diversity accessible through asymmetric synthetic processes. These attributes have previously been exploited in the synthesis of libraries via the Petasis reaction.1 Recently, diversity-oriented synthesis (DOS)2 has increasingly emphasized skeletal diversity involving the structural manipulation of scaffolds and synthesis of molecules with distinct skeletal framework.3 The allyl-cation rearrangement of dihydropyran 1 (Figure 1A) mediated by Sc(OTf)3 to yield the bispyran 2 illustrates how a rearrangement process may provide access to compounds that possess different shape characteristics. Three dimensional analysis of the two compounds using shape similarity and electrostatics was accomplished using OpenEye Scientific Software (http://www.eyesopen.com, OMEGA and ROCS). The shape fingerprint matching process4 (Figure 1B) characterized the Shape Tanimoto Score as 0.43 and the Tanimoto Electrostatics Score5 as <0.20. The overlay of the two compounds illustrates how the shape of the two compounds is distinctly different, evidenced by the low similarity scores, and how scaffold rearrangements may be useful diversity-generating processes. However, sequences involving rearrangements or fragmentations are highly underdeveloped and should continue to receive attention. We seek to develop synthetic sequences for the creation of novel cyclic scaffolds for library development featuring novel stereoselective processes. Our approach involves methodologies such as skeletal rearrangements, photochemical-mediated electrocyclic processes, cycloaddition reactions, and ring annulations as routes towards accessing skeletal diversity. In particular, photochemical reactions are highly underdeveloped in diversity oriented synthesis and are very promising for the generation of complex ring systems. An important aspect of functional diversity in the construction of libraries, in which the quality of diversity is optimal for any given scaffold, is the ability to vary the relative position of diversity elements. Mindful of this design criterion, the topology of target molecules will also be varied by the preparation of structures and scaffolds through efficient and stereoselective rearrangement processes. This approach will optimally display functionality as positional diversity elements. Moreover, the reagents and building blocks employed in the synthesis of library members will be custom building materials available from other methodologies available to the CMLD-BU through the various research groups in order to access the greatest chemical diversity available from the Center's resources. In is anticipated that the combination of novel structural rearrangement processes and the use of novel reagents will result in the construction of library compounds rich in chemical functionality, shape diversity, and topologically unique frameworks. Ultimately, the synergistic efforts of the participating researchers of the CMLD-BU will enhance the level of molecular complexity accessible in library construction.